Synthesis of Asymmetric Ionic Hybrid Detergents enables Micelles with Scalable Properties including Cell Compatibility.

ABSTRACT

Ionic detergents enable applications and cause harm in biospheres due to cell toxicity. The utility of covalent combinations between ionic and non-ionic detergent headgroups in modulating cell toxicity remains speculative due to the yet rarely explored synthesis. We close this gap and establish the modular synthesis of ionic/non-ionic hybrid detergents. We restructure a combinatorial methallyl dichloride one-pot coupling into a two-step coupling, which reduces by-products, improves product yields, and enables the gram-scale preparation of asymmetric, cationic/non-ionic and anionic/non-ionic hybrid detergents. Our modular synthesis delivers new modalities for the design of ionic detergents, including an unprecedented scaling of properties that determine applications, such as charge, critical micelle concentration, solubilizing properties, hard water tolerance, and cell compatibility. We uncover that shielding the charge in ionic headgroups can switch the detergent species that is toxic to cells from monomers to mixtures of monomers and micellar assemblies. Establishing the chemistry of ionic/non-ionic hybrid detergents provides a missing evolutionary link in the structural comparison of ionic and non-ionic detergents, enables an easy synthesis access to yet unexplored chemical spaces of asymmetric hybrid materials, and delivers new modalities for designing the toxicity of supramolecular nanomaterials.